Efficacy and safety of pyrotinib combined with albumin-bound paclitaxel as first-line treatment for HER2-positive metastatic breast cancer in patients previously treated with adjuvant and/or neoadjuvant trastuzumab therapy: The stage 1 results of a single-arm, phase 2 prospective clinical trial.

OBJECTIVE: It has been observed that the prognosis of patients with HER2-positive metastatic breast cancer has improved significantly with HER2-targeted agents. However, there is still a lack of evidence regarding first-line anti-HER2 treatment options for patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2-positive metastatic breast cancer. Besides, there are no reliable markers that can predict the efficacy of anti-HER2 treatment in these patients. METHODS: Patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2-positive metastatic breast cancer were enrolled. Pyrotinib plus albumin-bound paclitaxel were used as first-line treatment. The primary endpoint was the objective response rate (ORR). The safety profile was also assessed. In order to explore predictive biomarkers using Olink technology, blood samples were collected dynamically. RESULTS: From December 2019 to August 2023, the first stage of the study involved 27 eligible patients. It has not yet reached the median PFS despite the median follow-up being 17.8 months. Efficacy evaluation showed that the ORR was 92.6%, and the DCR was 100%. Adverse events of grade 3 or higher included diarrhoea (29.6%), leukopenia (11.1%), neutropenia (25.9%), oral mucositis (3.7%), and hand-foot syndrome (3.7%). Toll-like receptor 3 (TLR3) and Proto-oncogene tyrosine-protein kinase receptor (RET) were proteins with significant relevance to PFS in these patients. CONCLUSIONS: This study demonstrates that pyrotinib plus albumin-bound paclitaxel as a first-line treatment regimen shows good efficacy and manageable safety for patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2-positive metastatic breast cancer. Besides, a significant association was identified between the expression levels of TLR3 and RET and the PFS in patients.

Enhanced remediation of chlorpyrifos-contaminated soil by immobilized strain Bacillus H27.

Chlorpyrifos is a pesticide widely used in agricultural production with a relatively long residual half-life in soil. Addressing the problem of residual chlorpyrifos is of universal concern. In this study, rice hull biochar was used as an immobilized carrier to prepare the immobilized strain H27 for the remediation of chlorpyrifos-contamination soil. Soil microorganisms after remediation were investigated by ecotoxicological methods. The immobilized strain H27 had the highest removal rate of chlorpyrifos when 10% bacterial solution was added to the liquid medium containing 0.075-0.109 mm diameter biochar cultured for 22 hr. This study on the removal of chlorpyrifos by immobilized strain H27 showed that the initial concentration of chlorpyrifos in solution was 25 mg/L, and the removal rate reached 97.4% after 7 days of culture. In the soil, the removal rate of the immobilized bacteria group increased throughout the experiment, which was significantly higher than that of the free bacteria and biochar treatment groups. The Biolog-ECO test, T-RFLP and RT-RCR were used to study the effects of the soil microbial community and nitrogen cycling functional genes during chlorpyrifos degradation. It was found that ICP group had the highest diversity index among the four treatment groups. The microflora of segment containing 114 bp was the dominant bacterial community, and the dominant microflora of the immobilized bacteria group was more evenly distributed. The influence of each treatment group on ammonia-oxidizing bacteria (AOB) was greater than on ammonia-oxidizing archaea (AOA). This study offers a sound scientific basis for the practical application of immobilized bacteria to reduce residual soil pesticides.

Comparison of transoral vestibular robotic thyroidectomy with traditional low-collar incision thyroidectomy.

Transoral vestibular robotic thyroidectomy can really make the patient's body surface free of scar. This study aimed to compare the surgical and patient-related outcomes between the transoral vestibular robotic thyroidectomy and traditional low-collar incision thyroidectomy. The clinical data of 120 patients underwent transoral vestibular robotic thyroidectomy (TOVRT) or traditional low-collar incision thyroidectomy (TLCIT) were collected from May 2020 to October 2021. Propensity score matching analysis was used to minimize selection bias. All these patients were diagnosed with papillary thyroid carcinoma (PTC) through ultrasound-guided fine-needle aspiration prior to surgical intervention and surgical plan was tailored for each patient. An intraoperative recurrent laryngeal nerve (RLN) detection system was used in all patients, whose RLNs were identified and protected. We performed transoral vestibular robotic thyroidectomy with three intraoral incisions. Additional right axillary fold incisions were adopted occasionally to enhance fine reverse traction of tissue for radical tumor dissection. Clinical data including gender, age, tumor size, BMI, operation time, postoperative drainage volume and time, pain score, postoperative length of stay (LOS),number of lymph nodes removed, complications, and medical expense were observed and analyzed. Propensity score matching was used for 1:1 matching between the TOVRT group and the TLCIT group. All these patients accepted total thyroidectomy(or lobectomy) plus central lymph node dissection and all suffered from PTC confirmed by postoperative pathology. No conversion to open surgery happened in TOVRT group. The operative time of TOVRT group was longer than that of TLCIT group (P < 0.05). The postoperative drainage volume of TOVRT group was more than that of TLCIT group (P < 0.05). The drainage tube placement time of TOVRT group were longer than that of TLCIT group (P < 0.05). Significant differences were also found in intraoperative bleeding volume, pain score and medical expense between the two groups (P < 0.05). The incidence of perioperative common complications such as hypoparathyroidism and vocal cord paralysis in the two groups was almost identical (P > 0.05). However, there were some specific complications such as surgical area infection (one case), skin burn (one case), oral tear (two cases), and paresthesia of the lower lip and the chin (two cases) were found in TOVRT group. Obviously, the postoperative cosmetic effect of the TOVRT group was better than TLCIT group (P < 0.05). TOVRT is safe and feasible for low to moderate-risk PTC patients and is a potential alternative for patients who require no scar on their neck. Patients accepted TOVRT can get more satisfaction and have less psychologic injury caused by surgery.

Characteristics of biological manganese oxides produced by manganese-oxidizing bacteria H38 and its removal mechanism of oxytetracycline.

Oxytetracycline (OTC) is widely used in clinical medicine and animal husbandry. Residual OTC can affect the normal life activities of microorganisms, animals, and plants and affect human health. Microbial remediation has become a research hotspot in the environmental field. Manganese oxidizing bacteria (MnOB) exist in nature, and the biological manganese oxides (BMO) produced by them have the characteristics of high efficiency, low cost, and environmental friendliness. However, the effect and mechanism of BMO in removing OTC are still unclear. In this study, Bacillus thuringiensis strain H38 of MnOB was obtained, and the conditions for its BMO production were optimized. The optimal conditions were determined as follows: optimal temperature = 35 °C, optimal pH = 7.5, optimal Mn(Ⅱ) initial concentration = 10 mmol/L. The results show that BMO are irregular or massive, mainly containing MnCO3, Mn2O3, and MnO2, with rich functional groups and chemical bonds. They have the characteristics of small particle size and large specific surface area. OTC (2.5 mg/L) was removed when the BMO dosage was 75 µmol/L and the solution pH was 5.0. The removal ratio was close to 100 % after 12 h of culture at 35 °C and 150 r/min. BMO can adsorb and catalyze the oxidation of OTC and can produce ·O2-, ·OH, 1O2, and Mn(Ⅲ) intermediate. Fifteen products and degradation pathways were identified, and the toxicity of most intermediates is reduced compared to OTC. The removal mechanism was preliminarily clarified. The results of this study are convenient for the practical application of BMO in OTC pollution in water and for solving the harm caused by antibiotic pollution.

Biodegradation mechanism of chlorpyrifos by Bacillus sp. H27: Degradation enzymes, products, pathways and whole genome sequencing analysis.

Chlorpyrifos (CP) is a pesticide widely used in agricultural production. However, excessive use of CP is risky for human health and the ecological environment. Microbial remediation has become a research hotspot of environmental pollution control. In this study, the effective CP-degrading strain H27 (Bacillus cereus) was screened from farmland soil, and the degradation ratio was more than 80%. Then, the degradation mechanism was discussed in terms of enzymes, pathways, products and genes, and the mechanism was improved in terms of cell motility, secretory transport system and biofilm formation. The key CP-degrading enzymes were mainly intracellular enzymes (IE), and the degradation ratio reached 49.6% within 30 min. The optimal pH for IE was 7.0, and the optimal temperature was 25 °C. Using DFT and HPLC‒MS analysis, it was found that degradation mainly involved oxidation, hydrolysis and other reactions, and 3 degradation pathways and 14 products were identified, among which TCP (3,5,6-trichloro-2-pyridinol) was the main primary degradation product in addition to small molecules such as CO2 and H2O. Finally, the whole genome of strain H27 was sequenced, and the related degrading genes and enzymes were investigated to improve the metabolic pathways. Strain H27 had perfect genes related to flagellar assembly and chemotaxis and tended to tolerate CP. Moreover, it can secrete esterase, phosphatase and other substances, which can form biofilms and degrade CP in the environment. In addition, CP enters the cell under the action of permeases or transporters, and it is metabolized by IE. The degradation mechanism of CP by strain H27 is speculated in this study, which provided a theoretical basis for enriching CP-degrading bacteria resources, improving degradation metabolic pathways and mechanisms, and applying strain H27 to environmental pollution remediation.

Effects of the polyhalogenated carbazoles 3-bromocarbazole and 1,3,6,8-tetrabromocarbazole on soil microbial communities.

Soil ecosystems are being more contaminated with polyhalogenated carbazoles (PHCZs), which raising much attention about their impact on soil microorganisms. 3-Bromocarbazole (3-BCZ) and 1,3,6,8-tetrabromocarbazole (1,3,6,8-TBCZ) are two typical PHCZs with high detection rates in the soil environment. However, ecological risk research on these two PHCZs in soil is still lacking. In the present study, after 80 days of exposure, the ecological influence of 3-BCZ and 1,3,6,8-TBCZ was investigated based on 16S rDNA sequencing, ITS sequencing, gene (16S rDNA, ITS, amoA, nifH, narG and cbbL) abundance and soil enzyme activity. The results showed that the bacterial 16S rDNA gene abundance significantly decreased under 3-BCZ and 1,3,6,8-TBCZ exposure after 80 days of incubation. The fungal ITS gene abundance significantly decreased under 1,3,6,8-TBCZ (10 mg/kg) exposure. PHCZs contributed to the alteration of bacteria and fungi community abundance. Bacteria Sphingomonas, RB41 and fungus Mortierella, Cercophora were identified as the most dominant genera. The two PHCZs consistently decreased the relative abundance of Sphingomonas, Lysobacter, Dokdonella, Mortierella and Cercophora etc at 80th day. These keystone taxa are related to the degradation of organic compounds, carbon metabolism, and nitrogen metabolism and may thus have influence on soil ecological functions. Bacterial and fungal functions were estimated using functional annotation of prokaryotic taxa (FAPROTAX) and fungi functional guild (FUNGuild), respectively. The nitrogen and carbon metabolism pathway were affected by 3-BCZ and 1,3,6,8-TBCZ. The soil nitrogen-related functions of aerobic ammonia oxidation were decreased but the soil carbon-related functions of methanol oxidation, fermentation, and hydrocarbon degradation were increased at 80th day. The effects of 3-BCZ and 1,3,6,8-TBCZ on the abundances of the amoA, nifH, narG, and cbbL genes showed a negative trend. These results elucidate the ecological effects of PHCZs and extend our knowledge on the structure and function of soil microorganisms in PHCZ-contaminated ecosystems.

Feasibility of Telehealth Occupational Therapy for Behavioral Symptoms of Adults With Dementia: Randomized Controlled Trial.

IMPORTANCE: Supporting community residency of adults with Alzheimer's disease (AD) is a critical public health initiative. Occupational therapy can contribute to this goal. OBJECTIVE: To assess the feasibility of a novel telehealth intervention to support occupational engagement in community-residing people with AD. DESIGN: Single-blind, three-arm, parallel, randomized controlled trial. SETTING: Occupational therapy delivered through telehealth in participants' homes. PARTICIPANTS: People with AD who reside in the community with behavioral symptoms and their care partners (dyads). INTERVENTIONS: (1) HARMONY (Helping older Adults cReate & Manage OccupatioNs successfully), a telehealth intervention that applies principles of individualized guided discovery with environmental cueing for caregivers of persons with AD to promote activity participation and manage behavioral symptoms; (2) standardized training regarding the use of a sensory-based approach in dementia care; and (3) a control, including home safety education and weekly monitoring of behaviors. OUTCOMES AND MEASURES: Feasibility was assessed as the primary outcome measured by completion of at least 75% of the telehealth sessions. Secondary outcomes included change in functional activity performance and neuropsychiatric behavioral symptoms. RESULTS: Twenty-eight dyads participated. The intervention was feasible, with high adherence to weekly visits (M number of visits = 5.4 for HARMONY, 4.9 for standardized training, and 4.6 for control), with high participant retention in the intervention arms. HARMONY demonstrated promise in improving patient performance and behavioral symptoms. CONCLUSIONS AND RELEVANCE: HARMONY is feasibly delivered through telehealth service and has a positive effect on occupational performance and behavioral symptoms of AD. Additional studies are needed to explore effectiveness in a broader population. What This Article Adds: Use of HARMONY for community-residing adults with AD is feasible and has promise for improving functional activity performance and behavioral symptoms, as well as caregiver satisfaction.

Remove Artifacts from a Single-Channel EEG Based on VMD and SOBI.

With the development of portable EEG acquisition systems, the collected EEG has gradually changed from being multi-channel to few-channel or single-channel, thus the removal of single-channel EEG signal artifacts is extremely significant. For the artifact removal of single-channel EEG signals, the current mainstream method is generally a combination of the decomposition method and the blind source separation (BSS) method. Between them, a combination of empirical mode decomposition (EMD) and its derivative methods and ICA has been used in single-channel EEG artifact removal. However, EMD is prone to modal mixing and it has no relevant theoretical basis, thus it is not as good as variational modal decomposition (VMD) in terms of the decomposition effect. In the ICA algorithm, the implementation method based on high-order statistics is widely used, but it is not as effective as the implementation method based on second order statistics in processing EMG artifacts. Therefore, aiming at the main artifacts in single-channel EEG signals, including EOG and EMG artifacts, this paper proposed a method of artifact removal combining variational mode decomposition (VMD) and second order blind identification (SOBI). Semi-simulation experiments show that, compared with the existing EEMD-SOBI method, this method has a better removal effect on EOG and EMG artifacts, and can preserve useful information to the greatest extent.

A comparative study of two robotic thyroidectomy procedures: transoral vestibular versus bilateral axillary-breast approach.

OBJECTIVE: To compare the surgical outcomes between the transoral-vestibular robotic thyroidectomy (TOVRT) and bilateral axillo-breast approach robotic thyroidectomy (BABART). METHODS: A total of 99 patients with papillary thyroid carcinoma but no distant metastasis were enrolled in this study from May 2020 to April 2021. Lobectomy or total thyroidectomy with central lymph node dissection were performed in all cases. All 99 patients were received an ultrasound guided fine needle aspiration biopsy prior to surgical intervention, out of which 49 patients underwent TOVRT, while rest 50 patients underwent BABART. During the procedure, intraoperative neuromonitoring system was used and all recurrent laryngeal nerves (RLNs) were preserved, additionally for TOVRT procedure, three intraoral ports or right axillary fold incision was used to allow for fine countertraction of tissue for radical oncological dissection. The clinical data including age, gender, height, weight, BMI, primary tumor size, number of central lymph node removed, central lymph node metastasis, operating time, total hospital stays, postoperative hospital stays, total postoperative drainage volume, postoperative pain score, cosmetic effect and complications were recorded and analyzed. RESULTS: There were no significant differences in gender, height, weight, BMI and removed central lymph nodes between the two groups (P > 0.05). Patients accepted TOVRT were younger and had smaller primary tumor size than those who accepted BABART. The TOVRT group had a longer surgical time than the BABART group, but with smaller postoperative drainage volume and superior cosmetic effect (under visual analogue scale, VAS) (P < 0.05). There was no significant difference in lymph node metastasis, hospital stay and postoperative pain score (under numerical rating scale, NRS) between the two groups (P > 0.05). Last but not least, certain peculiar complications were observed in TOVRT group: paresthesia of the lower lip and the chin (one case), surgical site infection (one case) and skin burn (one case). CONCLUSION: Transoral-vestibular robotic thyroidectomy is safe and feasible for certain patients, which could be considered an alternative approach for patients who require no scarring on their neck.

The Emerging Landscapes of Long Noncoding RNA in Thyroid Carcinoma: Biological Functions and Clinical Significance.

Thyroid carcinoma (TC) is one of the most prevalent primary endocrine tumors, and its incidence is steadily and gradually increasing worldwide. Accumulating evidence has revealed the critical functions of long noncoding RNAs (lncRNAs) in the tumorigenesis and development of TC. Many TC-associated lncRNAs have been documented to be implicated in TC malignant behaviors, including abnormal cell proliferation, enhanced stem cell properties and aggressiveness, and resistance to therapeutics, through interaction with proteins, DNA, or RNA or encoding small peptides. Therefore, further elucidating the lncRNA dysregulation sheds additional insights into TC tumorigenesis and progression and opens new avenues for the early diagnosis and clinical therapy of TC. In this review, we summarize the abnormal expression of lncRNA in TC and the fundamental characteristics in TC tumorigenesis and development. Additionally, we introduce the potential prognostic and therapeutic significance of lncRNAs in TC.

DNASE1L2, as a Carcinogenic Marker, Affects the Phenotype of Breast Cancer Cells Via Regulating Epithelial-Mesenchymal Transition Process.

Purpose: The authors explore the role of DNASE1L2 in breast cancer (BC) and its affect on the cell phenotype. Methods: Breast invasive ductal carcinoma RNA-Seq data set was downloaded from The Cancer Genome Atlas database for analyzing DNASE1L2 levels. Overall survival curve was plotted by Kaplan-Meier methods. The correlations between DNASE1L2 expression and clinical characteristics were analyzed by chi-square tests. Cox regression models were implemented for analyzing the potential prognosticators of BC. Small interference RNA-DNASE1L2 and pcDNA3.1-DNASE1L2 were transfected into BC cells to silence and overexpress DNASE1L2, respectively. Relative mRNA and protein levels were determined by quantitative real-time PCR (qRT-PCR) and Western blot, respectively. Cell counting Kit-8, clone formation, and Transwell assays were employed to measure the proliferative, invasive, and migratory abilities. Results: Bioinformatics analysis showed that the levels of DNASE1L2 were found to be elevated in BC tissues, which was further proved by qRT-PCR tests. Besides, high expression of DNASE1L2 was dramatically led to a poor overall survival. Furthermore, DNASE1L2 expression was remarkably associated with age and pathologic-stage. Silencing DNASE1L2 showed an inhibitory effect on the proliferation, invasion, and migration of MCF7 cells, whereas overexpression of DNASE1L2 in BT549 cells presented the opposite results. Mechanistically, downregulation of DNASE1L2 could significantly enhance the levels of E-cadherin, as well as suppress the levels of Vimentin, N-cadherin and Snail, whereas upregulation of DNASE1L2 showed the reverse outcomes. Conclusion: This study for the first time demonstrated that DNASE1L2 was upregulated in BC cells, and acted as an oncogene to affect the phenotype of BC cells by modulating the epithelial-mesenchymal transition process, which suggested that DNASE1L2 might be considered as a useful biomarker for BC therapeutics.

Robotic lateral cervical lymph node dissection via bilateral axillo-breast approach for papillary thyroid carcinoma: a single-center experience of 260 cases.

To evaluate the feasibility and safety of robotic lateral cervical lymph node dissection via BABA, 260 thyroid cancer patients with suspected level II, III, IV, and Vb lymph node metastasis were selected. The lateral cervical compartment was exposed by splitting the sternocleidomastoid muscle longitudinally, and separating between the strap muscles and the anterior margin of the sternocleidomastoid muscle. The procedure was completed in 260 patients. Mean time for robotic lateral node dissection took 80 ± 21 min. The wound catheter was removed 6.3 days. Postoperative transient symptomatic hypocalcemia was observed in 51 patients, transient hoarseness in three, seroma in three, chyle leakage in two, and tracheal injury in one. 124 patients were confirmed to have lymph node metastasis on final pathological report. Average postoperative hospital stay was 6.5 days. Robotic lateral neck dissection by BABA is the acceptable operative alternative for thyroid cancer patients who wished to keep their surgical history private.

Adaptive sliding mode control for 4-wheel SBW system with Ackerman geometry.

In this paper, the modeling of front wheels Steer-by-Wire (SBW) system is further developed into 4-wheel SBW (4WSBW) system for electric vehicles with Ackerman Geometry taken into consideration. Moreover, a novel adaptive integral terminal sliding mode control (AITSMC) scheme is presented to control the wheel steering angles in both single-wheel situation and four-wheel situation. Based on Lyapunov criterion, stability proof guarantees that the tracking error in closed-loop converges to zero in finite time. In comparison with Proportional-Integral-Derivative (PID) based control, terminal sliding mode control (TSMC) and adaptive TSMC (ATSMC), the proposed control scheme only requiring information of the inertia of the wheels and the motors possesses two major advantages. First, robustness and finite-time convergence are ensured without obtaining information of disturbances caused by road conditions and parameters of viscous friction. Second, tracking error is further suppressed with noise impact in feedback loop caused by sensors while maintaining fast convergence rate. The synthesized performance of the 4WSBW vehicles is significantly improved and numerical simulations are conducted on the dynamic model of the system to corroborate the merits of the proposed control scheme.

Exploring an in situ LED-illuminated isothermal micro-calorimetric method to investigating the thermodynamic behavior of Chlorella vulgaris during CO2 bio-fixation.

Much endeavor has been dispensed recently to evaluate the potential of CO2 mitigation by microalgae. We introduce an alternative, novel, LED-illumination isothermal microcalorimetric method to assess the thermodynamic behaviors of microalgae for better understanding of their carbon sequestration capacity. Microalgae thermodynamic behaviors were recorded as power-time curves, and their indices such as total heat evolution (QT), maximum power output (Pmax) and heat generated by per algae cell (JN/Q) were obtained. The values for highest (74.80 g L-1) and control sample (0.00 g L-1) of QT, Pmax and JN/Q were 20.85 and 2.32 J; 252.17 and 57.67 µW; 7.91 × -06 and 8.80 × -07 J cell-1, respectively. According to the values of QT, a general order to promote the CO2 sequestration was found at 74.8 g L-1 > 29.92 g L-1 > 14.96 g L-1 > 7.48 g L-1 > 0 g L-1 of C sources, which directly corresponded to carbon availability in the growth medium. Chlorella vulgaris GIEC-179 showed the highest peak Pmax at 74.8 g L-1 concentration which was directly transformed to their biomass during bio-fixation of CO2 process. This study is applicable for better understanding of CO2 fixation performance of algae.